Total Cotinine in Plasma: A Stable Biomarker for Exposure to Tobacco Smoke

Abstract

Determination of plasma cotinine concentration is the predominant assay employed to quantify smoking and exposure to environmental tobacco smoke in epidemiological studies. However, cotinine is biotransformed into secondary metabolites. This pilot study determined plasma concentrations of cotinine, cotinine glucuronide, 3-hydroxycotinine, and 3-hydroxycotinine glucuronide. Total cotinine concentration was determined by summation of all four metabolites. The goals of this study were (1) to explore the stability and validity of total cotinine concentration as a measure of tobacco smoking and as a measure of exposure to environmental tobacco smoke in nonsmokers, (2) to explore the stability of plasma concentrations of each of the four nicotine metabolites in smokers by performing a.m. and p.m. measures, and (3) to explore the stability of indices of glucuronidation as measures of possible markers for enzymatic activity. The subject sample included 76 white volunteers (32% smokers and 68% nonsmokers). Plasma total cotinine concentration appeared to be very stable, suggesting that total cotinine concentration may be a good measure for epidemiological studies employing a single plasma sample. Moreover, plasma total cotinine concentration also reflected exposure to environmental tobacco smoke more accurately than did plasma cotinine concentration, which would have not identified 27% of passive smokers. 3-Hydroxycotinine glucuronide and 3-hydroxycotinine plasma concentrations were almost as stable as cotinine concentrations. However, cotinine glucuronide and its indices of glucuronidation were unstable, suggesting that cotinine glucuronide undergoes deconjugation. New studies of total cotinine in plasma using more than two blood collections during the day are needed to definitively establish that it is a stable biomarker for epidemiological studies.

Metabolism and Disposition Kinetics of Nicotine

“…The distribution of glucuronidation was unimodal in whites. Polymorphic pattern of cotinine glucuronidation in blacks has been detected in other studies (de Leon et al, 2002). Slower metabolism of cotinine explains in part the higher cotinine levels per cigarette detected in blacks compared with whites (Wagenknecht et al, 1990;English et al, 1994;Ahijevych and Gillespie, 1997;Caraballo et al, 1998).…”

Relationship of Human Toenail Nicotine, Cotinine, and 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol to Levels of These Biomarkers in Plasma and Urine

“…Systemic exposure to cigarette smoke is commonly monitored by measuring nicotine and its major metabolite cotinine in urine, saliva, blood, and hair (4)(5)(6)(7)(8)(9)(10)(11)(12). In some studies, trans-3 ¶-hydroxycotinine, the major metabolite of cotinine, is used along with nicotine and cotinine to estimate total nicotine uptake and exposure (13)(14)(15).…”

Mass Spectrometric Quantitation of Nicotine, Cotinine, and 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol in Human Toenails

“…Measurements of nicotine and cotinine levels in urine, saliva, and blood are commonly used to monitor systemic exposure to cigarette smoke in smokers and nonsmokers exposed to environmental tobacco smoke (ETS; refs. [6][7][8][9]. Urinary metabolites of NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (NNAL-Glucs), are excellent biomarkers of NNK uptake in rodents and humans (10,11).…”